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Developing a model system for teaching goniotomy.

PURPOSE: To design a model-system instruction course to prepare trainees for performing goniotomy on patients. DESIGN: Experimental study. PARTICIPANTS: Three pediatric ophthalmology fellows and 1 recent graduate of the fellowship program. METHODS: We piloted 3 model systems: human cadaver eyes with and without Marty the Surgical Simulator (Iatrotech Inc., Del Mar, CA, hereafter referred to as Marty Head) eye supporting system and artificial eyes in Marty Head. For improving intraocular view in cadaver eyes, we used epithelial scrapping, intracameral viscoelastic, and/or intracameral lubricating jelly. Each trainee underwent a training course, including background reading, didactic lecture, and video review followed by goniotomy on model systems with the operating microscope. MAIN OUTCOME MEASURES: Each trainee evaluated each step of the course using modified 5-point Likert scales. Reading material and videos were evaluated for usefulness, readability/quality, and new information obtained. Each model system was evaluated for visibility, ease of setup, surgical feel, and transferability to live surgery. In the end, each trainee was asked to assess the overall course for usefulness. RESULTS: Trainees rated the reading materials and video highly for their usefulness and quality, yet they believed they did not learn substantial amounts of new information. Visibility and ease of setup was best with artificial eyes in the Marty Head model. Human cadaver eyes in the Marty Head provided somewhat less visibility and ease of setup, but the perceived feel and transferability to live surgery was slightly better than with artificial eyes. Cadaver eyes without the Marty Head got the lowest rating in all categories. At the end of the course, all participants felt more confident and ready to perform goniotomy on patients. All recommended this course as part of pediatric ophthalmology fellowship training programs. CONCLUSIONS: This model system instruction course can assist trainees in learning to perform goniotomy while potentially lessening the risks to patients.

Gonioscopy↗

The impact of fiducial distribution on headset-based registration in image-guided sinus surgery.

OBJECTIVE: The objective of this study was to assess registration error due to fiducial configuration for the ENT headsets for the CBYON Suite (CBYON, Mountain View, CA) and InstaTrak (GEMS Navigation and Visualization, Waukesha, WI). STUDY DESIGN: Axial CT scans (1-mm slice thickness) were obtained of for 24 cadaveric heads using the CBYON headset and for 23 cadaveric heads using the GEMS headset. The CBYON and GEMS NAV software were used to calculate the fiducial registration error (FRE). Fiducial localization error (FLE) was estimated from FRE. Theoretical target registration error (TRE) was calculated at 11 targets. RESULTS: The FRE for CBYON and GEMS NAV was 0.69 mm and 0.27 mm, respectively. The theoretical TRE for CBYON and GEMS NAV was 0.41 mm and 0.30 mm, respectively. The theoretical TRE was greater at targets posterior in the sinus cavities. CONCLUSION: Theoretical TRE values for both ENT headsets are less than clinically observed TRE. Clinically observed TRE is likely due to repositioning accuracy. EBM RATING: B-2.

Cadaver↗

Redox signaling in central neural regulation of cardiovascular function.

One of the most prominent concepts to emerge in cardiovascular research over the past decade, especially in areas focused on angiotensin II (AngII), is that reactive oxygen species (ROS) are critical signaling molecules in a wide range of cellular processes. Many of the physiological effects of AngII are mediated by ROS, and alterations in AngII-mediated redox mechanisms are implicated in cardiovascular diseases such as hypertension and atherosclerosis. Although most investigations to date have focused on the vasculature as a key player, the nervous system has recently begun to gain attention in this field. Accumulating evidence suggests that ROS have important effects on central neural mechanisms involved in blood pressure regulation, volume homeostasis, and autonomic function, particularly those that involve AngII signaling. Furthermore, oxidant stress in the central nervous system is implicated in the neuro-dysregulation associated with some forms of hypertension and heart failure. The main objective of this review is to discuss the recent progress and prospects for this new field of central redox signaling in cardiovascular regulation, while also addressing the molecular tools that have spurred it forward.

Angiotensin II↗

Nitric oxide and homeostatic control: an intercellular signalling molecule contributing to autonomic and neuroendocrine integration?

Accumulated evidence indicates that nitric oxide (NO) plays a pivotal role in the central control of bodily homeostasis, including cardiovascular and fluid balance regulation. Two major neuronal substrates mediating NO actions in the control of homeostasis are the paraventricular nucleus (PVN) of the hypothalamus, considered a key center for the integration of neuroendocrine and autonomic functions, and the supraoptic nucleus (SON). In this work, a comprehensive review of NO modulatory actions within the SON/PVN, including NO actions on neuroendocrine and autonomic outputs, as well as the cellular mechanisms underlying these effects is provided. Furthermore, this review comprises recent progress from our laboratory that adds to our current understanding of the cellular sources, targets and mechanisms underlying NO actions within neuroendocrine and autonomic hypothalamic neuronal circuits. By combining in vitro patch clamp recordings, tract-tracing neuroanatomy, immunohistochemistry and live imaging techniques, we started to shed light into the cellular sources and signals driving NO production within the SON and PVN, as well as NO actions and mechanisms targeting discrete neuronal populations within these circuits. Based on this new information, we have expanded one of the current working models in the field, highlighting a key role for NO as a signaling molecule that facilitates crosstalk among various cell types and systems. We propose that this dynamic NO signaling mechanisms may constitute a neuroanatomical and functional substrate underlying the ability of the SON and PVN to coordinate complex neuroendocrine and autonomic output patterns.

Animals↗

Aplysia seductin is a water-borne protein pheromone that acts in concert with attractin to stimulate mate attraction.

Mate attraction in Aplysia involves the long-distance water-borne protein pheromones attractin, enticin, and temptin which are released during egg-laying. Other water-borne pheromones are predicted to act in concert with attractin, enticin, and temptin, but their identities were unknown. We recently identified a highly expressed Aplysia californica albumen gland gene (Alb-23) that encoded a novel protein by differential library screening of an albumen gland cDNA library. To determine whether Alb-23 ('seductin') was a water-borne pheromone, we employed Western blot analysis, purification and expression of albumen gland proteins, immunolocalization studies, pheromone secretion assays, comparative genomics, and behavioral bioassays. Immunoreactive seductin was detected in eluates of egg cordons, indicating that seductin was secreted onto the cordon during egg laying. Aplysia brasiliana seductin was 94% identical to its A.californica homolog. In T-maze attraction assays, the combination of attractin and seductin was significantly attractive to potential mates, whereas either protein alone was not. Data from this and previous studies support the hypothesis that seductin is a water-borne protein pheromone that acts in concert with attractin, enticin, and temptin to attract Aplysia to form and maintain mating aggregations.

Amino Acid Sequence↗

A technique for making a diagnostic and surgical template.

Implant-supported restorations can restore function and esthetics provided that the implants are placed in the predetermined location and properly angulated. This article describes the fabrication of a diagnostic template incorporating a silicone radiopaque marker as a guide for achieving 3-dimensional evaluation of bone without artifacts using computed tomography. The diagnostic template may be easily transformed into a surgical template by removing the silicone marker.

Dental Implantation, Endosseous↗

Surgical templates for prosthetically guided implant placement.

The article describes a prosthetically guided method for the fabrication of surgical templates for partially edentulous patients. A number of stainless steel components are used to capture the optimal prosthetic position for the placement of the implant determined from a diagnostic arrangement. A radiopaque stainless steel guide sleeve is used to guide the drill in preparation of the osteotomy after radiographs are made to verify the position and proposed trajectory of the guide sleeve.

Acrylic Resins↗

The fabrication and use of an extraoral surgical guide for implant placement coincident with soft tissue matrix expansion grafts: a clinical report.

During soft tissue matrix expansion (tent pole) graft (STMEG) surgery, the traditional intraoral surgical guide for dental implant placement cannot be used because the surgery is initiated and maintained outside the oral cavity. The essential records established from an intraoral surgical guide must be transferred to an extraoral surgical guide. This clinical report describes the fabrication and use of an extraoral surgical guide employed during STMEG surgery.

Acrylic Resins↗

Computational predictions of pulmonary blood flow gradients: gravity versus structure.

A computational model of blood flow through the human pulmonary arterial tree has been developed to investigate the mechanisms contributing to regional pulmonary perfusion in the isolated network when the lung is in different orientations. The arterial geometric model was constructed using a combination of computed tomography and a volume-filling branching algorithm. Equations governing conservation of mass, momentum, and vessel distension, incorporating gravity, were solved to predict pressure, flow, and vessel radius. Analysis of results in the upright posture, with and without gravity, and in the inverted, prone, and supine postures reveals significant flow heterogeneity and a persistent decrease in flow in the cranial and caudal regions for all postures suggesting that vascular geometry makes a major contribution to regional flow with gravity having a lesser role. Results in the isolated arterial tree demonstrate that the vascular path lengths and therefore the positioning of the pulmonary trunk relative to the rest of the network play a significant role in the determination of flow.

Algorithms↗

Modeling dynamic reciprocity: engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation.

In order to understand why cancer develops as well as predict the outcome of pharmacological treatments, we need to model the structure and function of organs in culture so that our experimental manipulations occur under physiological contexts. This review traces the history of the development of a prototypic example, the three-dimensional (3D) model of the mammary gland acinus. We briefly describe the considerable information available on both normal mammary gland function and breast cancer generated by the current model and present future challenges that will require an increase in its complexity. We propose the need for engineered tissues that faithfully recapitulate their native structures to allow a greater understanding of tissue function, dysfunction, and potential therapeutic intervention.

Animals↗

Three-dimensional co-culture models to study prostate cancer growth, progression, and metastasis to bone.

Cancer-stromal interaction results in the co-evolution of both the cancer cells and the surrounding host stromal cells. As a consequence of this interaction, cancer cells acquire increased malignant potential and stromal cells become more inductive. In this review we suggest that cancer-stromal interaction can best be investigated by three-dimensional (3D) co-culture models with the results validated by clinical specimens. We showed that 3D culture promoted bone formation in vitro, and explored for the first time, with the help of the astronauts of the Space Shuttle Columbia, the co-culture of human prostate cancer and bone cells to further understand the interactions between these cells. Continued exploration of cancer growth under 3D conditions will rapidly lead to new discoveries and ultimately to improvements in the treatment of men with hormonal refractory prostate cancer.

Animals↗

Genomic profiling of acquired resistance to apoptosis in cells derived from human atherosclerotic lesions: potential role of STATs, cyclinD1, BAD, and Bcl-XL.

Current theories suggest that atherosclerosis, plaque rupture, stroke, and restenosis after angioplasty may involve defective apoptotic mechanisms in vascular cells. Prior work has demonstrated that cells from human atherosclerotic lesions, and cells from the aorta of aged rats, exhibit functional resistance to apoptosis induced by TGF-beta and glucocorticoids. The present studies demonstrate that human lesion-derived cells (LDC) are also resistant to apoptosis induced by fas ligation compared to cells derived from the adjacent media, and that in vitro expansion of LDC causes acquired resistance to apoptosis. Microarray profiling of fas-resistant versus sensitive cells identified a set of genes including STATs, caspase 1, cyclin D1, Bcl-xL, VDAC2, and BAD. The STAT proteins have been implicated in resistance to apoptosis, potentially via their ability to modulate caspase 1 (ICE), Bcl-xL, and cyclin D1 expression. Western blot analysis of sensitive and resistant LDC clonal lines confirmed increases in cyclin D1, STAT6, Bcl-xL, and BAD, with decreased expression of caspase 1. Thus, transcript profiling has identified a potential pathway of apoptotic regulation in subsets of lesion cells. The resistant phenotype may contribute to plaque stability and excessive vascular repair, while sensitive cells may be involved in plaque rupture and infarction. The data suggests both genetic interventions and novel small-molecule inhibitors that may be effective modulators of apoptosis in atherosclerosis, angina, and in-stent restenosis.

Apoptosis↗

Factors affecting accuracy of in vitro valvar pressure gradient estimates by Doppler ultrasound.

Doppler ultrasound is used successfully in clinical situations for noninvasive measurement of pressure changes across stenotic cardiac valves. However, situations that might lead to errors in measurement have not been identified. This study determines the effect of flow rate, viscosity, orifice shape and size on the calculation of Doppler transvalvar gradient. Pressure gradient is usually computed from the equation P1-P2 = 4 X Vmax2, where P1-P2 is the gradient and Vmax is the maximal jet velocity measured by Doppler ultrasound. An in vitro model was developed with interchangeable orifices that permitted the jet to be detected by an in-line Doppler transducer. The model allowed alteration of flow rates, viscosities and pressure gradients. When P1-P2 as predicted by Doppler was compared with that measured by manometers (PM), excellent correlations were obtained for triangular orifices of areas as small as 78.5 mm2 (r = 0.95) and for circular and elliptical orifices to as small as 50.2 mm2 (r = 0.99). For smaller orifices, P1-P2 correlated poorly with PM. Good correlation was found between P1-P2 and PM, with flow rates ranging from 0.7 to 8.4 liters/min (r = 0.97) with a 10-mm diameter circular orifice (area = 78.5 mm2). No observable differences were found in the accuracy of the equation between high and low flow rates. Viscosity had no effect on the accuracy of the P1-P2 comparison with PM over the range evaluated (1 to 10 cp). It is concluded that the modified Bernoulli Doppler gradient equation provides accurate results in the usual clinical situation when an orifice permits true jet formation.

Blood Flow Velocity↗

An optical model to describe image contrast with bifocal intraocular lenses.

We attempted to quantify the decrease in contrast associated with the concentric-style bifocal intraocular lens by using a model eye and bifocal intraocular lens, with a model unifocal intraocular lens as a control. When imaging near objects, pupils smaller than 2.5 mm produced image contrast of 100% of the control; larger pupils degraded contrast to 25% for a 6-mm pupil. For distant objects, pupils smaller than 2.5 mm produced image contrast of 70% to 95% because of the pinhole effect; larger pupils engaged the distance portion of the intraocular lens and maintain 80% contrast on average. Thus, the bifocal intraocular lens produced image contrast greater than 70% in all situations tested, except when imaging near objects with a pupil larger than 3.5 mm. The data suggest that image contrast is highly dependent on pupil size and object distance.

Contrast Sensitivity↗